The molecular basis of target cell recognition by NK cells is poorly understood. Unlike T and B cells, NK cells do not rearrange DNA to generate diversity. Therefore, one could predict that NK cells might express several receptors to recognize various targets or utilize some other mechanism to generate diversity. In fact, over the last few years a number of receptors have been identified on NK cells (Lanier 1998). However, all the function of NK cells could not be accounted by the known receptors.
The C-type carbohydrate recognition domain (CRD) is the common feature among Cat++ dependent animal lectins and structurally related proteins. A subset of the C-type lectin family found on natural killer (NK) cells contains domains homologous to other C-type lectin domains, but whether they mediate interactions through carbohydrate or protein binding remains unresolved (Weis et al. 1998). NK cell receptors with lectin-like domains are encoded in the NK gene complex on Chromosome (Chr) 6 in the mouse and Chr 12 in the human. (Brown et al. 1997; Yabe et al. 1993; Yokoyama and Seaman 1993).
The majority of NK cell receptors encoded by the NK gene complex belong to groups of highly related genes such as the NKR-P1, Ly-49, and NKG2 families. The Ly-49 and NKG2 families contain members that are mostly inhibitory, but have a few members that transduce activation signals (Lanier 1998; Long and Wagtmann 1997; Yokoyama and Seaman 1993). The NKR P1 receptors have been observed to act as activating receptors in rodents. Cross-linking of the human NKR-P1 homologue with antibody leads to inconsistent results (Lanier 1998). CD94 is a type II receptor express on most NK cells and was originally implicated as an inhibitory receptor (Change et al. 1995; Long and Wagtmann 1997). Subsequently, it was discovered to form a heterodimer with members of the NKG2 family (Lazetic et al. 1996).
CD69 and AICL (activation-induced C-type lectin) are two structurally similar receptors localized to the NK gene complex, but have interesting differences from the other genes located there. As opposed to the other type II receptors in the NK gene complex, which are restricted to NK cells and a subset of T cells, CD69 and AICL are expressed in most cells of hematopoetic origin (Hamann et al. 1997; Lanier 1998; Long and Wagtmann 1997; Testi et al. 1994). The function of AICL is not know, but CD69, cross-linking leads to the activation of NK cells, T cells, B cells, monocytes, granulocytes, and platelets (Testi et al. 1994). In addition, these genes appear to have single rather than multiple isoforms.
Despite advances that have been made in the area of immune cell function, a need continues to exist in the medical arts for improved techniques for antibody tumor growth and other cancer forms such as leukemia. In addition, insofar as bone-marrow grating has been used, significant immune rejection difficulties preclude the use of these. techniques for improving and/or replacing immune function in animals, and most importantly, preventing host rejection.